Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial
Introduction Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.Methods and a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-05-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/5/e068606.full |
| _version_ | 1797831140474617856 |
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| author | Isik S Johansen Christian Østergaard Andersen Thomas Benfield Pernille Ravn Birgitte Lindegaard Sandra Tingsgård Simone Bastrup Israelsen Louise Thorlacius-Ussing Karina Frahm Kirk Andreas Knudsen Suzanne Lunding |
| author_facet | Isik S Johansen Christian Østergaard Andersen Thomas Benfield Pernille Ravn Birgitte Lindegaard Sandra Tingsgård Simone Bastrup Israelsen Louise Thorlacius-Ussing Karina Frahm Kirk Andreas Knudsen Suzanne Lunding |
| author_sort | Isik S Johansen |
| collection | DOAJ |
| description | Introduction Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.Methods and analysis Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.Ethics and dissemination The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration number ClinicalTrials.Gov:NCT04291768. |
| first_indexed | 2024-04-09T13:47:16Z |
| format | Article |
| id | doaj.art-a309e041f64247a79b0523c4285c8f62 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-09T13:47:16Z |
| publishDate | 2023-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-a309e041f64247a79b0523c4285c8f622023-05-09T01:30:06ZengBMJ Publishing GroupBMJ Open2044-60552023-05-0113510.1136/bmjopen-2022-068606Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trialIsik S Johansen0Christian Østergaard Andersen1Thomas Benfield2Pernille Ravn3Birgitte Lindegaard4Sandra Tingsgård5Simone Bastrup Israelsen6Louise Thorlacius-Ussing7Karina Frahm Kirk8Andreas Knudsen9Suzanne Lunding108 Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Clinical Microbiology, Hvidovre Hospital, Hvidovre, Denmark3 Danish Medical Journal, Copenhagen, Denmark8 Department of Gynecology and Obstetrics, Odense University Hospital, Odense, DenmarkCentre for Physical Activity Research (CFAS), Copenhagen University Hospital - Rigshospitalet, Copenhagen, DenmarkCenter of Research and Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, DenmarkCenter of Research and Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, DenmarkCenter of Research and Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, DenmarkDepartment of Infectious Diseases, Aalborg University Hospital, Aalborg, DenmarkDepartment of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DenmarkDepartment of Internal Medicine, Section for Infectious Diseases, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, DenmarkIntroduction Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.Methods and analysis Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.Ethics and dissemination The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration number ClinicalTrials.Gov:NCT04291768.https://bmjopen.bmj.com/content/13/5/e068606.full |
| spellingShingle | Isik S Johansen Christian Østergaard Andersen Thomas Benfield Pernille Ravn Birgitte Lindegaard Sandra Tingsgård Simone Bastrup Israelsen Louise Thorlacius-Ussing Karina Frahm Kirk Andreas Knudsen Suzanne Lunding Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial BMJ Open |
| title | Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial |
| title_full | Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial |
| title_fullStr | Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial |
| title_full_unstemmed | Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial |
| title_short | Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial |
| title_sort | short course antibiotic treatment of gram negative bacteraemia gnb5 a study protocol for a randomised controlled trial |
| url | https://bmjopen.bmj.com/content/13/5/e068606.full |
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